{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:47:45Z","timestamp":1777362465544,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytopathology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Melanoma is an aggressive malignancy with a high propensity for metastasis, and approximately 3% of cases present as melanoma of unknown primary (MUP), posing diagnostic and management challenges. We report a 63\u2010year\u2010old man who presented with painful, rapidly enlarging axillary and cervical lymphadenopathy without an identifiable cutaneous lesion. Fine\u2010needle aspiration (FNA) of an axillary lymph node revealed a hypercellular specimen composed of highly pleomorphic malignant cells with prominent nucleoli and abundant cytoplasm. Immunocytochemistry demonstrated diffuse nuclear SOX10 expression and focal Melan\u2010A positivity, with negative pancytokeratin staining, supporting a diagnosis of melanoma. Subsequent excisional biopsy confirmed metastatic melanoma with concordant SOX10 and S100 immunoreactivity. Comprehensive genomic profiling detected genomic alterations, including\n                    <jats:italic>BRAF<\/jats:italic>\n                    (K601E),\n                    <jats:italic>MAP2K2<\/jats:italic>\n                    (E207K),\n                    <jats:italic>TP53<\/jats:italic>\n                    (W146*) and a\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter \u2010146C&gt;T mutation, along with\n                    <jats:italic>CDKN2A\/B<\/jats:italic>\n                    loss and\n                    <jats:italic>MYC<\/jats:italic>\n                    amplification; no\n                    <jats:italic>KIT<\/jats:italic>\n                    or\n                    <jats:italic>NRAS<\/jats:italic>\n                    mutations were detected. Tumour mutational burden (TMB) was 18 mutations\/Mb, and the tumour was microsatellite stable. This case highlights the clinical utility of a cytology\u2010first diagnostic workflow for MUP, in which FNA combined with a targeted immunohistochemical panel enables rapid lineage confirmation and facilitates timely surgical excision and molecular testing. Integration of cytologic diagnosis with genomic analysis provides a practical, real\u2010world approach to precision oncology in complex metastatic presentations of melanoma.\n                  <\/jats:p>","DOI":"10.1111\/cyt.70080","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:59:39Z","timestamp":1777359579000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytology\u2010First Diagnostic Workflow for Melanoma of Unknown Primary With Molecular Profiling"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1378-4476","authenticated-orcid":false,"given":"Hong","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mokhtar","family":"Abdelhammed","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nisha S.","family":"Ramani","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Baylor College of Medicine  Houston Texas USA"},{"name":"Pathology &amp; Immunology Michael E. DeBakey VA Medical Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22757"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jasc.2025.06.002"},{"issue":"28","key":"e_1_2_7_4_1","article-title":"The Bethesda System for Reporting Cervical Cytology","volume":"19","author":"Pangarkar M. A","year":"2022","journal-title":"CytoJournal"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jmp5020015"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22832"},{"issue":"94","key":"e_1_2_7_7_1","article-title":"Reimagining Cytopathology in the Molecular Era: Integration or Fragmentation?","volume":"22","author":"Das S.","year":"2025","journal-title":"Cytojournal"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.627527"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2020-206962"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0036"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.05.036"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050092"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-2054"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1026"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.23.00670"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14312"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001134"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.13818"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230062"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1502583"},{"issue":"4","key":"e_1_2_7_21_1","first-page":"1071","article-title":"Cutaneous Melanoma: from Pathogenesis to Theralpy (Review)","volume":"52","author":"Leonardi G. C.","year":"2018","journal-title":"International Journal of Oncology"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15562"}],"container-title":["Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.70080","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cyt.70080","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.70080","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:59:41Z","timestamp":1777359581000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.70080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":21,"alternative-id":["10.1111\/cyt.70080"],"URL":"https:\/\/doi.org\/10.1111\/cyt.70080","archive":["Portico"],"relation":{},"ISSN":["0956-5507","1365-2303"],"issn-type":[{"value":"0956-5507","type":"print"},{"value":"1365-2303","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"assertion":[{"value":"2026-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cyt.70080"}}